Neoadjuvant External Beam Radiation Research Articles

Neoadjuvant radiotherapy followed by hysterectomy in locally advanced endometrial cancer: Outcomes from a tertiary government hospital in the Philippines

ObjectiveManaging endometrial cancer with suspected or gross cervical involvement lacks a standard approach. This study evaluated outcomes in patients with cervical and/or parametrial involvement treated with neoadjuvant radiation followed by hysterectomy. MethodsFourteen patients from 2007 to 2022 with locally advanced endometrial cancer and cervical and/or parametrial involvement were retrospectively analyzed. They received neoadjuvant external beam radiotherapy (45–50.4 Gy in 25–30 fractions) and high-dose rate brachytherapy (5.5–7.0 Gy per fraction in 3–4 fractions), followed by extrafascial hysterectomy. Clinical data, pathologic response, and survival outcomes were assessed, along with factors associated with pathologic response. ResultsMost patients (86%) had stage III disease with cervical extension, 93% had parametrial involvement, and 14% had nodal involvement. Chemotherapy was given to 86% either concurrently or adjuvantly. Post-surgery, 86% had no pathologic cervical involvement, and 93% had negative surgical margins. Pathologic complete response was seen in 43%. Locoregional recurrence occurred in 14%. Median follow-up was 30 months, with recurrence-free survival and overall survival rates of 86% and 100%, respectively. Lower grade tumors significantly correlated with pathologic complete response (Φ = 0.72, p = 0.026). No significant correlation was found between pathologic complete response and other factors. No late grade 3–4 toxicities were reported. ConclusionNeoadjuvant radiation followed by hysterectomy, with or without chemotherapy, is a viable strategy for managing endometrial cancer with cervical and/or parametrial involvement. This approach enhances resectability, yielding high rates of pathologic complete response and negative resection margins, showing promise for this challenging patient group.

Impact of dose distribution by a 3D planning system for brachytherapy with 198Au grains for head and neck cancer.

There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198Au grains for head and neck cancer was evaluated. Thirty-two patients who were treated with 198Au grains for head and neck cancer were reviewed. Twenty-five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy. With a median observation period of 60 months, the 5-year local control rate was 82.9%. V85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001). Dose distribution with 198Au grains can predict local control and late adverse events.

Abstract P1-10-06: Carcinoma en Cuirasse Secondary to Locally Advanced Breast Carcinoma: a case report

Abstract Introduction & Objective This report highlights an unusual presentation of skin metastasis of inflammatory breast cancer that resembles a rare condition called Carcinoma en Cuirasse (CeC). CeC was first described by anatomist Alfred Velpeau in 1838 when he observed how the coalescing nodules and diffuse sclerodermoid induration found on the chest and abdomen in CeC resembled the medieval steel breastplate or a cuirasse. Case Presentation A 62-year-old female presented to the emergency department for evaluation of a palpable left breast mass and concurrent skin lesions for the past 5 months. Based on the erosion of the nipple, chest CT, as well as core needle and skin biopsy, a diagnosis of stage IV (cT4d, cN3, cM1) ER+, PR-, HER2/neu- advanced/inflammatory breast carcinoma was made. The patient underwent a 20-week course of neoadjuvant chemotherapy followed by 25 treatments of neoadjuvant external beam radiotherapy (EBRT) with a total dose of 5000cGy to the left breast and the regional lymph node due to disease progression after 4 cycles of neoadjuvant chemotherapy. She proceeded to bilateral modified radical mastectomy and bilateral lymph node involvement was found, and later disease progressed with skin involvement outside the EBRT treatment field. Additional 25 treatment of palliative radiotherapy was utilized with another 5000cGy, followed by 2 months of chemotherapy to provide better palliation and quality of life. Upon completion of therapy, a unique skin metastasis pattern was noticed. Shortly afterward the patient passed away from severe sepsis secondary to multiple wounds infected by drug-resistant Pseudomonas aeruginosa followed by Clostridium difficile colitis. Conclusion This case shows clinical characteristics of Carcinoma en Cuirasse and provides important considerations for more research to be done to highlight the unique pattern of skin metastasis following radiation and the potential use for radiation to treat chemotherapy-resistant skin metastasis from recurrent invasive breast carcinoma. Citation Format: Chung-Tang Liu, Keri Lanier. Carcinoma en Cuirasse Secondary to Locally Advanced Breast Carcinoma: a case report [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-06.

Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma

A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

Does Timing Matter? Surgical Outcomes in High-Grade Sarcomas after Neoadjuvant Radiation Therapy

BackgroundThe impact of time to surgical resection after neoadjuvant external beam radiation therapy (EBRT) in the high-grade soft tissue and retroperitoneal sarcomas has not been well established. We aimed to evaluate how surgical timing from EBRT affects oncologic and perioperative outcomes. MethodsWe performed a single institution retrospective cohort study of patients with biopsy-proven, high-grade sarcoma who completed neoadjuvant EBRT and resection from January 1, 1999 to September 1, 2018. We collected demographic and clinicopathologic variables, stratifying patients by time interval between EBRT and surgery: <6, 6-8, 8-10, and >10 wk. Primary outcomes collected were as follows: disease-free survival, overall survival, and perioperative complications. ResultsOf the 269 patients identified, 146 met inclusion criteria. The median follow-up was 24 mo. Overall and local recurrence were 37% (n = 54) and 14.4% (n = 21), respectively. Time to surgery did not affect recurrence (P = 0.82) or survival (P = 0.88). Positive margins (odds ratio 2.7, confidence interval 1.14, 6.51, P < 0.05) were predictive of recurrence. Primary tumor location, surgical timing, histology, and intraoperative radiation therapy were not associated with differences in recurrence. The overall complication rate was 28%, with 63% from wound infections. Fewer postoperative complications occurred in the < 6-wk cohort versus > 6-wk cohort (15% versus 38%, P < 0.05). ConclusionsWe found no difference in oncologic outcomes associated with the timing of surgical resection after EBRT. Patients undergoing resection >6 wk were at higher risk for all complications without impacting wound complication rates. Future studies may include preoperative optimization of patients requiring delays in surgical planning to decrease perioperative complication rates.

Locally unresectable differentiated thyroid cancer: outcomes and perspectives.

Differentiated thyroid cancer (DTC) patients with an unresectable primary tumor cannot benefit from curative surgery, and radioiodine treatment for locoregional and distant disease is not possible with the thyroid gland still in place. Due to local invasion, these patients cannot be included in clinical trials, so that treatment options are limited. The aim of this study was to describe the characteristics and the prognosis of patients with these locally unresectable DTC. A retrospective and multicentric analysis of consecutive cases of unresectable DTC diagnosed between 2000 and 2015 was performed. The study population consisted in 22 patients, 13 females (59%); median age: 77 years (range: 52-91). Thyroid tumors were papillary in six, follicular in seven, Hürthle cell in one and poorly differentiated in eight patients. Patients were treated with external beam radiation therapy (EBRT) (57%), locoregional therapy of distant metastases (41%), cytotoxic chemotherapy (38%) and tyrosine kinase inhibitors (TKIs) (33%). TKI treatment resulted in median disease control duration of 7 months with a grade 3-4 toxicity rate of 44%. Only one patient had a total thyroidectomy after neo-adjuvant EBRT. The 1, 3 and 5-year cumulative survival rate was 81%, 27.7% and 21.5%, respectively. The cause of death was DTC in 11 cases (local progression in 7), and to other causes in 7 cases; no patient died from treatment toxicity. Clinical trials and approved treatments are lacking for unresectable DTC. TKI treatment may allow prolonged disease control with acceptable toxicity.

Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy

BackgroundNeoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT.MethodsWe retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS).ResultsA total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4–17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40–50.4 Gy]) and IORT (median dose: 15 Gy [15–17 Gy]). The median age was 65 years [33–82]. The median follow-up was 23 months [0–63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively).ConclusionsIORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.

Neoadjuvant Chemoradiation Therapy Followed by Extrafascial Hysterectomy in Locally Advanced Type II Endometrial Cancer Clinically Extending to Cervix

PurposeThe role of neoadjuvant chemoradiation therapy in locally advanced type II endometrial cancer is controversial. We thus aimed to present our experience with the hypothesis that neoadjuvant chemoradiation therapy is associated with similarly high rates of downstaging and locoregional control for type II endometrial cancer and type I endometrial cancer. Methods and MaterialsThirty-four patients with type II endometrial cancer with clinical evidence of cervical ± parametrium involvement treated with neoadjuvant external beam radiation therapy (45-50.4 Gy in 25-28 fractions) and high-dose-rate brachytherapy with a median total dose of 20 Gy (range, 15-27.5) in 4 fractions (range, 3-5) and concurrent platinum chemotherapy ± adjuvant chemotherapy from 2008 to 2018 were retrospectively reviewed. Patients with type I pathologic diagnoses and those treated with definitive (rather than preoperative) intent were excluded. ResultsPathologic characteristics were as follows: 38% were carcinosarcoma, 18% serous, and 24% clear cell. Ninety-four percent of patients were downstaged to an extrafascial hysterectomy, and 94% had negative surgical margins. The 2-year local control, regional control, distant control, disease-free survival, and overall survival were 87.8%, 81.3%, 76.3%, 52.5%, and 63.7%, respectively. There was 1 subacute grade 3 and 1 late grade 3 small bowel obstruction, directly attributable to radiation therapy. ConclusionsNeoadjuvant chemoradiation therapy effectively downstages the majority of locally advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins.

Is there a place for liver transplantation in cases with unresectable central cholangiocarcinoma?

Central cholangiocarcinoma represents a very aggressive malignancy associated with poor survival rats especially due to the fact that most patients are diagnosed in advanced stages of the disease when curative resection is no longer feasible. In order to try improving the long-term outcomes of these patients, especially in unresectable cases liver transplantation has been proposed with promising results. This is a literature review of the largest studies focused on this subject. Cholangiocarcinomas remain aggressive tumors with poor outcomes whenever surgery with curative intent is not feasible. Currently, the largest experience accumulated consists of neoadjuvant external beam radiotherapy in association with beam radiation, 5 fluorouracil and capecitabine followed by orthotopic liver transplantation. Following this therapeutic protocol excellent long-term outcomes have been reported even if vascular involvement is present.

Neoadjuvant external beam radiation is associated with No benefit in overall survival for early stage pancreatic cancer

ObjectiveNeoadjuvant protocols for early stage pancreatic adenocarcinoma (PDAC) frequently involve external beam radiation used in combination with systemic chemotherapy. The benefit of radiation in these protocols has not been determined. MethodsWe examined patients with stage I and II PDAC within the National Cancer Data Base between 2006 and 2012. Propensity score matching was used to compare patients receiving neoadjuvant chemotherapy including radiation (NCRT) to those receiving neoadjuvant chemotherapy without radiation (NCT) prior to pancreaticoduodenectomy. ResultsPrior to matching, NCRT patients had higher rates of T3 tumors (P = 0.046) and vascular abutment (P < 0.001). Propensity score matching (1:1) yielded 397 patients per group. Patients treated with NCRT were more likely to have node negative resections (P < 0.001) but had increased rates of 90-day mortality (P = 0.015) and demonstrated a trend towards shorter overall survival (P = 0.0502) than those receiving NCT. ConclusionIn early stage PDAC, the addition of radiation to NCT is often utilized with more advanced disease and is associated with higher perioperative mortality and no long-term overall survival benefit.

Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable intermediate- and high-risk prostate cancer.

41 Background: Despite evidence of prolonged survival when adding androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) in men with unfavorable intermediate- and high-risk prostate cancer (PC), some of these men are not receiving ADT. We explored whether comorbidity can explain this discrepancy given the observation that survival may be shortened in men with moderate to severe comorbidity who receive ADT. Methods: Between 10/1997 and 5/2013, 3,348 men with unfavorable intermediate- (2,380 patients; 70.7%) or high-risk (986 patients; 29.3%) PC were treated at the Prostate Cancer Foundation of Chicago using brachytherapy with or without neoadjuvant EBRT and/or ADT, and formed the study cohort. A multivariable logistic regression analysis was used to evaluate whether comorbidity (history of congestive heart failure [CHF] and/or myocardial infarction [MI]) was associated with decreased odds of ADT use in men with unfavorable intermediate- or high-risk PC, adjusting for age, PC prognostic factors, year of brachytherapy, and EBRT use. Results: Among patients with unfavorable-intermediate-risk PC, 31.2% received ADT, and in the high-risk cohort, 38.3%, 12.3%, and 4.8% received up to 6, &gt;6-18, or &gt;18 months of ADT respectively. In men with high-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use of any duration (all p values &gt;0.71), but the odds of ADT use decreased over time (adjusted odds ratio (AOR) 0.87, 95% confidence interval (CI) [0.83,0.91], p&lt;0.0001; AOR 0.93, 95% CI [0.87,0.99], p=0.023; AOR 0.92, 95% CI [0.83,1.01], p=0.089, for up to 6, &gt;6-18, and &gt;18 months respectively, with no ADT as the reference). Similarly, in men with unfavorable intermediate-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use (p=0.49), whereas the odds of ADT use decreased significantly over time (AOR 0.96, 95% CI [0.94,0.98], p=0.0009). Conclusions: While ADT use has decreased over time in men with unfavorable intermediate- and high-risk PC undergoing brachytherapy with or without supplemental EBRT, this decrease does not appear to be occurring in men with a history of CHF or MI.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria

PurposeFor locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Materials and methodsRetrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45–50.4Gy in 25–28 fractions) and image-based HDR brachytherapy (5–5.5Gy times 3–4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. ResultsAll patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0–153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. ConclusionsNeoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5–5.5Gy times 3–4 fractions, for a cumulative EQD2 of 60–70Gy, is well tolerated with high rates of clinical and pathological response.

Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.

The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <5 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p = 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.

Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.

322 Background: The use of intensity modulated radiation therapy (IMRT) has allowed for the administration high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neoadjuvant external beam radiation (EBRT) therapy using IMRT. Methods: This is a retrospective study of 21patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed according to the CTCAE v. 3 criteria. Results: The actuarial 3 and 5-year OS and LRFS was 66% and 51%, 57% and 41% respectively. Factors predictive for LRFS were microscopically negative margins (p=0.022), a median tumor diameter &lt; 15 cm (p=0.007) and a pathology of liposarcoma (p=0.021); however, patients treated for recurrent disease fared worse (p=0.04). As for OS, grade 1 histology was a predictive factor for better outcome (p=0.05). EBRT was generally well tolerated. Acute gastrointestinal grade 1 or 2 toxicity occurred in 33% of patients and one patient had unexplained post-radiation grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented grade 1 gastrointestinal toxicity and one patient presented grade 3 small bowel stenosis not clearly due to radiation toxicity. Conclusions: Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.

Intraoperative Electron Radiation Therapy (IOERT) in the management of locally recurrent rectal cancer

BackgroundTo evaluate disease control, overall survival and prognostic factors in patients with locally recurrent rectal cancer after IOERT-containing multimodal therapy.MethodsBetween 1991 and 2006, 97 patients with locally recurrent rectal cancer have been treated with surgery and IOERT. IOERT was preceded or followed by external beam radiation therapy (EBRT) in 54 previously untreated patients (median dose 41.4 Gy) usually combined with 5-Fluouracil-based chemotherapy (89%). IOERT was delivered via cylindric cones with doses of 10–20 Gy. Adjuvant CHT was given only in a minority of patients (34%). Median follow-up was 51 months.ResultsMargin status was R0 in 37%, R1 in 33% and R2 in 30% of the patients. Neoadjuvant EBRT resulted in significantly increased rates of free margins (52% vs. 24%). Median overall survival was 39 months. Estimated 5-year rates for central control (inside the IOERT area), local control (inside the pelvis), distant control and overall survival were 54%, 41%, 40% and 30%. Resection margin was the strongest prognostic factor for overall survival (3-year OS of 80% (R0), 37% (R1), 35% (R2)) and LC (3-year LC 82% (R0), 41% (R1), 18% (R2)) in the multivariate model. OS was further significantly affected by clinical stage at first diagnosis and achievement of local control after treatment in the univariate model. Distant failures were found in 46 patients, predominantly in the lung. 90-day postoperative mortality was 3.1%.ConclusionLong term OS and LC can be achieved in a substantial proportion of patients with recurrent rectal cancer using a multimodality IOERT-containing approach, especially in case of clear margins. LC and OS remain limited in patients with incomplete resection. Preoperative re-irradiation and adjuvant chemotherapy may be considered to improve outcome.

Acute Leukemias Following a Diagnosis of Colorectal Cancer: Are They Therapy-Related?

Abstract 1453▪▪This icon denotes a clinically relevant abstractApproximately 140,000 patients per year are diagnosed with colorectal cancer in the United States. Historically, treatment modalities have included surgery, 5-fluourouracil (5-FU) and/or radiation. Over the past ten years standard treatment has evolved and now includes platinum compounds such as Oxaliplatin, the topoisomerase I inhibitor Irinotecan, and the oral analogue of 5-FU, Capecitabine. Rectal cancer often utilizes these agents in a neoadjuvant fashion with concomitant radiation therapy, followed by surgery and postoperative chemotherapy. The incidence of therapy related acute myeloid leukemia (t-AML) has been well described after treatment for breast cancer and lymphoma and occurs most commonly in patients previously treated with alkylating agents or topoisomerase II-active agents (epipodophylotoxins or anthracyclines). However, the occurrence of acute leukemia after a diagnosis of colorectal cancer has never been systematically investigated in a large clinical database.Using ICD-9 codes for leukemia and colorectal cancer, we identified 37 patients seen at Memorial Sloan-Kettering Cancer Center since 1970 with colon cancer, rectal cancer, or anal cancer who were subsequently diagnosed with leukemia or a myelodysplastic syndrome (MDS). Of these 37 patients, 23 had colon cancer, 13 had rectal cancer and 1 had anal cancer. Treatments for the primary malignancy included: external beam radiation alone (2), chemotherapy alone (10), chemotherapy in combination with radiation (12) and surgery alone (13). The most common leukemia was acute myeloid leukemia (20) followed by MDS (8), Pre-B cell acute lymphoblastic leukemia (ALL) (4), acute promyelocytic leukemia (APL) (3), T-ALL (1) and T- cell prolymphocytic leukemia (PLL) (1). Of the 8 patients with MDS, 4 had chronic myelomonocytic leukemia. Among patients who received chemotherapy or combined chemoradiation the most common chemotherapeutic agents were 5-Fluorouracil (19) followed by Oxaliplatin (8), intrahepatic Floxuridine (2), Irinotecan (1) and Mitomycin (1). The median time from treatment with chemotherapy and/or radiation to diagnosis of acute leukemia or MDS was 41 months (range 10 months – 135 months). The most common cytogenetic abnormalities of the patients with MDS or AML were monosomies and deletions in chromosomes 5, 7, and 12. Of the 4 patients with Pre B-ALL, 3 had t(9;22). Interestingly of the 23 patients with myeloid leukemia, 3 (13%) patients developed the APL subtype with the disease defining t(15;17). Two of these three patients had received neo-adjuvant external beam radiation and 5-FU, one received adjuvant treatment with Oxaliplatinand one was treated with surgery alone. The latency period between diagnosis or treatment of colorectal cancer and the development of APL ranged from 10 to 20 years.Table 1Patient CharacteristicsM/F23/14Type of Lower GI MalignancyColon23Rectal13Anal1TreatmentSurgery Alone13Radiation Alone2Chemo-radiation12Chemotherapy Alone105-Fluorouracil19Oxaliplatin8Intrahepatic Floxuridine2Irinotecan1Mitomycin1Median Latency period (range)41 months (10-135 months)Type of leukemiaAML (non-APL)20APL3MDS4CMMOL4ALL Ph pos3ALL Ph neg1T-ALL1T-PLL1In conclusion, to our knowledge this is among the first uses of a comprehensive clinical database to investigate the occurrence of acute leukemia and MDS after the diagnosis and/or treatment of a colorectal or anal malignancy. Our finding that the most common chromosomal abnormalities seen in patients who developed MDS or AML involve chromosomes 5 and 7, similar to t-AML suggests, that some of these leukemias are therapy related. It may be that the widespread adoption of newer platinum compounds will precipitate t-AML. Future studies of larger databases of patients may help establish if the acute leukemias seen after colorectal cancer are related to prior exposure to anti-cancer therapy. Disclosures:Douer:Teva: Consultancy.

Neoadjuvant chemoradiation for potentially resectable gastric cancer.

e14724 Background: Outcomes are poor in patients with gastric cancer, and recurrence is common. Perioperative chemotherapy and adjuvant chemoradiation therapy (CRT) improve survival in patients with resectable disease. Experience with neoadjuvant CRT for potentially resectable disease is limited, and its role remains undefined. We report our experience using neoadjuvant CRT for potentially resectable gastric cancer. Methods: An IRB-approved, retrospective review from 1994 to 2007 identified 23 patients with biopsy-proven, potentially resectable gastric cancer. Patients had T2/T3 and/or N1 disease and no evidence of metastatic disease by endoscopic ultrasound and cross-sectional imaging. All underwent neoadjuvant external beam radiation with concurrent 5-FU or platinum-based chemotherapy followed by restaging and surgery if appropriate. Results: Of the 23 patients, 20 completed neoadjuvant CRT and surgical exploration. Two patients (n=2) had radiographic disease progression during neoadjuvant CRT and did not undergo resection. One patient (n=1) developed a perforated gastric ulcer during CRT and underwent emergent resection. The median time from diagnosis to surgery and completion of neoadjuvant CRT to surgery was 104 days and 37.5 days, respectively. Gastrectomy was performed in 17 (85%) patients who completed neoadjuvant CRT. Metastatic disease was identified in the remaining 3 (15%) patients. Following gastrectomy, a complete pathologic response was observed in 4 (23.5%) patients, a partial response in 11 (64.7%) patients, and no response was identified in 2 (11.8%) patients. One (6%) patient had microscopic positive margins, and 9 (53%) had positive lymph nodes. There was no perioperative mortality. Two (11.8%) patients had anastomotic leaks, which were managed non-operatively. The median length of stay was 10 days. The median disease-free survival was 10.5 months, and median overall survival was 19.6 months. Conclusions: Gastric cancer carries a poor prognosis. Surgical resection after neoadjuvant CRT has low treatment-associated morbidity and mortality. Survival and complete response rates are comparable to published series. Further evaluation of this treatment strategy is warranted to assess its efficacy.

Correlation in Rectal Cancer Between Clinical Tumor Response After Neoadjuvant Radiotherapy and Sphincter or Organ Preservation: 10-Year Results of the Lyon R 96-02 Randomized Trial

To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial. A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months. The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR <50% (p = 0.014). In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.

Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma

Purpose To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas. Materials/methods Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case. Results Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction ⩾ 50%) was highly predictive of a good pathological response ( p < 0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses. Conclusions Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response.

Low-Dose Neoadjuvant External Beam Radiation Therapy for Soft Tissue Sarcoma

For soft tissue sarcoma, neoadjuvant external beam radiation therapy (EBRT) to 50 Gy has the same local control (LC) and overall survival as postoperative radiation therapy (PORT) to 60 Gy, but with increased wound complications. We examined whether low-dose neoadjuvant EBRT would decrease acute toxicity while maintaining LC. From 1971 to 2008, 1,765 patients with nonmetastatic soft tissue sarcoma were treated with radiation therapy at Massachusetts General Hospital. We identified 42 patients treated with low-dose neoadjuvant EBRT (median, 20 Gy; range, 16-26) followed by surgical resection and PORT. PORT included EBRT (25 patients; median, 40 Gy; range, 20-56.2), brachytherapy (13 patients; median, 42 Gy; range, 26-50), and intraoperative radiation therapy (IORT) (4 patients; median, 12.5 Gy; range, 8-20). The median total dose was 63.3 Gy (range, 28-78.4). Median follow-up was 36 months (range, 4-318). Severe acute wound complications were reported in 15 patients (36%) and correlated to PORT technique (16% EBRT, 69% brachytherapy, 50% IORT, p = 0.004). The 5-year LC was 73% and correlated to PORT technique (68% EBRT, 100% brachytherapy, 50% IORT, p = 0.03) and histology (p = 0.05), with a trend to improvement if >60 Gy (p = 0.10). The 5-year overall survival was 65% and correlated to extent of resection (p < 0.001) and margin status (p < 0.001). Despite using low-dose neoadjuvant EBRT, we report a high rate of severe acute wound complications that was strongly associated with brachytherapy. Modification of the brachytherapy technique may decrease acute toxicity while maintaining excellent local control. Further study must be conducted before recommending broader application.